Overexpression of TRIP6 promotes tumor proliferation and reverses cell adhesion-mediated drug resistance (CAM-DR) via regulating nuclear p27Kip1 expression in non-Hodgkin’s lymphoma

Abstract

Recent studies have identified that thyroid hormone receptor-interacting protein 6 (TRIP6) is implicated in tumorigenesis. However, the functional role of TRIP6 in non-Hodgkin's lymphoma (NHL) has never been elucidated. In this study, we demonstrated that TRIP6 is reversely correlated with the clinical outcomes of NHL patients. Western blot and immunohistochemical analysis revealed that TRIP6 expression is lower in indolent lymphoma than in progressive lymphoma. Kaplan-Meier survival curves indicated that the upregulation of TRIP6 is significantly associated with poor overall survival. Moreover, patients with higher expression of TRIP6 are prone to shorter time to recurrence. Furthermore, we also found that TRIP6 can promote the proliferation of NHL cells via regulating cell cycle progression. In addition, adhesion of lymphoma cells to fibronectin (FN) decreased TRIP6 expression, which led to the upregulation of nuclear p27(Kip1) expression by decreasing phosphorylation of p27(Kip1) at T157. Importantly, overexpression of TRIP6 can reverse cell adhesion-mediated drug resistance (CAM-DR) phenotype in NHL. In summary, these results suggest that TRIP6 is a novel prognostic indicator for NHL patients and may shed new insights into the important role of TRIP6 in cancer development.

Silencing of LIMD1 promotes proliferation and reverses cell adhesion‑mediated drug resistance in non‑Hodgkin's lymphoma

“…Drug resistance remains an obstacle in achieving the optimal treatment of lymphoma (3). Increasing evidence has suggested that the bone marrow microenvironment protects lymphoma cells from apoptosis induced by cytotoxic drugs, including cell adhesion-mediated drug resistance (CAM-DR), leading to relapse following chemotherapy (5)(6)(7)(8). The emergence of CAM-DR remains a major obstacle for the successful treatment of lymphoma.…”

Upregulation of ADAM12 contributes to accelerated cell proliferation and cell adhesion-mediated drug resistance (CAM-DR) in Non-Hodgkin’s Lymphoma

“…The PI3K/AKT/mTOR pathway plays an important role on NHL growth and survival, data suggest that PI3Kδ inhibition can overcome prosurvival signals from the microenvironment that maintain NHL cells [4]. Lymphoma cells adhered to stromal cells are important in mediating tumor resistance to cytotoxic therapy (cell adhesion-mediated drug resistance (CAM-DR)) [5]. Previous studies have shown that the human bone marrow stromal cell adhered to Bcell lymphoma cells can protect NHL cells from rituximab cytotoxicity [6].…”

MiR‐485‐3p modulates neural stem cell differentiation and proliferation via regulating TRIP6 expression

“…TRIP6 is one member of zyxin family of the LIM proteins and is one focal adhesion element with the capacity to the shuttle between cell nucleus and surface . TRIP6 was played roles in modulation of signal transduction and actin dynamics during cell migration and adhesion . Increasing studies showed that TRIP6 was expressed in neurons of hippocampal and regulated biological function of neurological .…”

“…38,39 TRIP6 was played roles in modulation of signal transduction and actin dynamics during cell migration and adhesion. 40,41 Increasing studies showed that TRIP6…”